From the Guidelines
Docetaxel should be added to ADT and apalutamide in patients with metastatic castration-sensitive prostate cancer who have high-volume disease, characterized by visceral metastases or four or more bone lesions with at least one outside the vertebral column and pelvis. The standard regimen consists of docetaxel 75 mg/m² administered intravenously every 3 weeks for 6 cycles, alongside continuous ADT and apalutamide 240 mg daily. This triplet therapy should be initiated promptly after diagnosis of metastatic disease, as supported by the most recent guidelines from the National Comprehensive Cancer Network (NCCN) 1. Patients should receive premedication with dexamethasone before each docetaxel infusion to reduce the risk of hypersensitivity reactions and fluid retention. The addition of docetaxel to hormonal therapy in this setting has demonstrated significant survival benefits, with studies showing improved overall survival and delayed disease progression compared to ADT alone or ADT plus a single agent, as seen in the CHAARTED and STAMPEDE trials 1. Key considerations for initiating this treatment include:
- The presence of high-volume disease, which is a critical factor in determining the benefit of adding docetaxel to ADT and apalutamide 1
- The patient's fitness for chemotherapy, as this intensive approach may not be suitable for all patients, particularly the elderly or those with significant comorbidities
- The potential for increased adverse effects with the addition of docetaxel, which must be carefully managed to ensure the best possible outcomes for patients.
From the Research
Treatment of Metastatic Castration-Sensitive Prostate Cancer
- The treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC) has evolved over the past few years, with the addition of docetaxel or abiraterone acetate to androgen deprivation therapy (ADT) becoming standard of care 2.
- The effectiveness of docetaxel with ADT in a general population of patients with mCSPC was associated with poorer outcomes and high rates of toxicity compared to published studies 3.
Addition of Docetaxel to ADT and Apalutamide
- There is no direct evidence on when to add docetaxel to ADT and apalutamide (Erleada) in patients with mCSPC.
- However, studies suggest that treatment intensification with docetaxel improves outcomes, including survival, in men with mCSPC 4.
- The use of a "triplet systemic therapy," which consists of the combination of ADT, an androgen receptor pathway inhibitor (such as apalutamide), and docetaxel, may further improve outcomes, including survival 4.
Treatment Patterns and Outcomes
- Real-world data show that most patients with mCSPC initiating ADT receive ADT-only or ADT + nonsteroidal anti-androgen (NSAA), despite the emergence of docetaxel and novel hormonal therapies 5.
- Patients treated with ADT + NSAA had similar risks of castration-resistant disease and overall mortality as ADT-only 5.
- The addition of docetaxel to ADT has been shown to improve outcomes, including survival, in men with mCSPC, but the optimal timing of this addition is not well established 3, 2, 6.